Assuntos
Compostos Organometálicos/uso terapêutico , Parasitemia/tratamento farmacológico , Pentamidina/uso terapêutico , Tripanossomicidas/uso terapêutico , Tripanossomíase Africana/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos , Compostos Organometálicos/química , Pentamidina/análogos & derivados , Pentamidina/química , Relação Estrutura-Atividade , Taxa de Sobrevida , Tripanossomicidas/química , Trypanosoma brucei brucei/efeitos dos fármacos , Tripanossomíase Africana/mortalidadeRESUMO
The activities of 17 new rhodium drug complexes were determined against Leishmania donovani promastigotes. The five most active salts were selected: [Rh(III)(2-amino-6-ethoxybenzothiazole)(4)Br(2)](+)Br(-); [Rh(III)(2-bromothiazole)(4)(Br)(2)](+)Br(-); [Rh(III)(mefloquine)(4)(Cl)(2)](+)Cl(-); [Rh(III)(2-mepacrine)(4)(Cl)(2)](+)Cl(-), and [Rh(III)(oxamniquine)(4)(Cl)(2)](+)Cl(-), which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salts [Rh(III) (mefloquine)(4)(Cl)(2)](+)Cl(-), [Rh(III)(2-mepacrine)(4)(Cl)(2)](+)Cl(-) and [Rh(III)(oxaminquine)(4)(Cl)(2)](+)Cl(-) with a percentage of specific (15)Cr release of 49.3, 64.8 and 53.2% at 24 h of incubation and 100 microg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The ultrastructural studies in the flagellates treated with the salt [Rh(III)(2-amino-6-ethoxybenzothiazole)(4)Br(2)](+)Br(-) showed some alterations in the nucleus of the parasites with a very condensed chromatin and an electrodense endosome. This compound showed a high in vivo activity in parasitized Wistar rats.
Assuntos
Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Ródio/farmacologia , Ródio/uso terapêutico , Animais , Linhagem Celular , Cricetinae , Técnicas In Vitro , Leishmania donovani/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Mesocricetus , Ratos , Ratos Wistar , Ródio/químicaRESUMO
Anti-inflammatory activity and the effect on gastric damage of some copper(II) complexes has been investigated. In a preliminary screening the compounds were studied on the carrageenin paw edema model and two complexes showed inhibitory action on acute as well as subacute models of inflammation. This activity does not seem to be related to an inhibitory effect on prostaglandin biosynthesis or with leukocyte migration into inflamed tissue. These complexes showed an inhibitory effect on volume exudate in experimental pleurisy and on the production of superoxide anions. These inhibitory effects could explain, at least in part, their anti-inflammatory activity. Also, these complexes protected gastric mucosa against the damage induced by HCl and by oral administration of indometacin.
